Antidiabetic effect of 1-deazapurines derivatives with alpha-glucosidase Enzyme: A molecular tools approach

Abstract

Alpha-glucosidase inhibition has been shown by several 1-deazapurine derivatives that have already been synthesized and evaluated in vitro, providing a potential treatment target for type 2 diabetes. Six of them were shown to have higher percentages of inhibition against the alpha-glucosidase enzyme and lower IC50 values. The binding mechanism and stability of the generated complexes are investigated in the current work using various molecular modeling methodologies. The ligands L17, L11, and L4 present the best binding energy with the establishment of interaction toward the site active, based on the results of the molecular docking simulation. The stability of the chosen complexes was then validated using molecular dynamics simulation. However, ADME-T prediction and Drug-likeness results show that these compounds have promising pharmacokinetic properties and oral bioavailability. Finally, these results imply that compounds L4 and L11 are very promising as a target for creating a lead molecule for type 2 diabetes.